A claim you hear on longevity podcasts

Does high blood sugar switch off AMPK and sirtuins?

The claim checked: At high levels, glucose switches off the protective AMPK and sirtuins Hear it at 42:33

What do the studies say?

Not enough evidence

The one study found lower SIRT1 levels in type 2 diabetes, more so with poor glucose control. None here tests AMPK or glucose spikes.

Computed from 1 study that test this point, each judged by two readers, in full. Fewer than 3 sources so far. 1 more study is waiting for a full read and does not count yet.

What was said on the podcast?

“So, that's one keep those glucose levels down. But also what glucose is going to be doing to you at high levels is shutting off those protective mechanisms. Remember particularly AMPK and the sirtuins they get switched off by sugar.”
David Sinclair, Lifespan · What to Eat & When to Eat for Longevity | Lifespan with Dr. David Sinclair #2 · 42:33 on YouTube
Comes up in 4 episodes of the show.
Point 1 of 2 Not enough evidence

High glucose (spikes) switches off protective AMPK and sirtuins

Agree 0

None.

Partly agree 1

trial or observed group · 2013

“Notably, the SIRT1 level was consistently lower in patients with poor glycaemic control than in those with good glycaemic control (p < 0.01).”

Poor glycaemic control in type 2 diabetes patients reduces endothelial progenitor cell number by influencing SIRT1 signalling via platelet-activating factor receptor activation. Diabetologia
Who: 48 type 2 diabetic patients (25 poor, 23 good glycaemic control) and age-matched healthy controls; plus in-vitro EPCs from healthy donors
PMID 23070058

Disagree 0

None.

Point 2 of 2 Leaning for

Glucose attached to proteins (glycation) lowers longevity, gives type 2 diabetes and probably cardiovascular disease

All ten are observational and linked glycation markers such as HbA1c and AGEs to heart disease or death. Two clearly backed the claim; eight backed only part of it, in narrower groups, or with links that faded after adjustment.

Computed from 10 studies that test this point, each judged by two readers, in full. 9 more studies are waiting for a full read and do not count yet.

Agree 2

other primary study · 2021

“In conclusion, we showed that skin autofluorescence measurements significantly predicted new CVD events and mortality in people with type 2 diabetes independently of conventional cardiovascular risk factors.”

Skin autofluorescence predicts new cardiovascular disease and mortality in people with type 2 diabetes. BMC Endocr Disord
Who: 2,349 Dutch adults with type 2 diabetes from the Lifelines cohort (mean age 57, BMI 30.2)
PMID 33435948

trial or observed group · 2010 · landmark

“In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause as compared with fasting glucose.”

Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med
Who: Black or white middle-aged adults (mean age 56.7) without diagnosed diabetes or cardiovascular disease in four US communities (ARIC visit 2, 1990-1992)
PMID 20200384

Partly agree 8

other primary study · 2011

“Higher levels of AGEs are associated with incident fatal and nonfatal CVD as well as all-cause mortality in individuals with type 1 diabetes, independently of other risk factors and of several potential AGEs-related pathophysiological mechanisms.”

Higher plasma levels of advanced glycation end products are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study. Diabetes Care
Who: 339 adults with type 1 diabetes (169 with nephropathy, 170 normoalbuminuric), free of CVD at entry, Steno Diabetes Center
PMID 21270199

pooled analysis · 2017

“HbA1c is a reliable risk factor for all-cause mortality and cardiovascular mortality in both non-diabetic and diabetic populations.”

Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: a systematic review and meta-analysis. BMJ Open
Who: Adults aged 25-90 with and without diabetes in longitudinal observational cohorts from 20 countries
PMID 28760792

pooled analysis · 2012

“In conclusion, our results suggest that chronic hyperglycemia is associated with increased risks for cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes and independent from other conventional risk factors.”

Glycosylated hemoglobin in relationship to cardiovascular outcomes and death in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS One
Who: patients with type 2 diabetes in 26 prospective cohorts (US, UK, Finland, Netherlands, Sweden, Denmark, Italy, Germany, New Zealand, China), mostly primary care or clinic based
PMID 22912709

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other primary study · 2018

“Although most AGE associations did not remain significant after adjusting for major risk factors or history of CVD, higher concentrations of 3DG-H1 in combination with lower MetSO levels further enhanced risk for incident CVD in the VADT.”

Advanced Glycation End Products, Oxidation Products, and Incident Cardiovascular Events in Patients With Type 2 Diabetes. Diabetes Care
Who: Patients with type 2 diabetes: VADT subcohort (n = 445) and ACCORD lipid-trial nested case-control subgroup (n = 271); predominantly white, overweight/obese men with ~10-year diabetes duration
PMID 29208654

other primary study · 2009

“In this study, elevated serum AGEs, sRAGE, and esRAGE were predictive of cardiovascular disease mortality, and appeared to be predictive of all-cause mortality at a level of marginal significance.”

Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women. Aging Clin Exp Res
Who: Moderately to severely disabled community-dwelling women aged 65 and older in Baltimore (Women's Health and Aging Study I)
PMID 19448391

pooled analysis · 2018

“In summary, our study suggests that both continuous and categorical elevations in HbA 1c are associated with increased first‐ever ischemic stroke risk, irrespective of diabetes mellitus status.”

Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta-Analysis. J Am Heart Assoc
Who: Adults (≥18) with and without diabetes in cohort and nested case-control studies
PMID 29773578

pooled analysis · 2018

“Higher SAF levels were significantly associated with higher pooled risk estimates for cardiovascular mortality (HR: 2.06; 95% CI, 1.58–2.67) and all‐cause mortality (HR: 1.91; 95% CI, 1.42–2.56).”

Skin Autofluorescence-Indicated Advanced Glycation End Products as Predictors of Cardiovascular and All-Cause Mortality in High-Risk Subjects: A Systematic Review and Meta-analysis. J Am Heart Assoc
Who: Adults with diabetes, peripheral artery disease or chronic/end-stage kidney disease in prospective cohorts, mean age 45-73
PMID 30371199

pooled analysis · 2016

“A linear association of HbA1c levels with primary cardiovascular events was observed.”

HbA1c levels in non-diabetic older adults - No J-shaped associations with primary cardiovascular events, cardiovascular and all-cause mortality after adjustment for confounders in a meta-analysis of individual participant data from six cohort studies. BMC Med
Who: non-diabetic adults aged 50 and older from six population-based cohorts in Europe and the USA (ESTHER, SHIP, ELSA, Tromsø, KORA, NHANES)
PMID 26867584

Disagree 0

None.

What else was said but not tested?

  • Animals given lots of glucose and especially fructose get fatty liver disease and diabetes (speaker unclear)

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